PROJECT SUMMARY/ABSTRACT Growth hormone (GH) treatment is a paradigm of ?expansive biotechnology,? wherein a biomedical technology originally designed for treatment of disease (GH deficiency; GHD) expanded, with the encouragement of well- intended physicians and support of industry, into treatment of conditions that blur the boundary between disease and variation (idiopathic short stature; ISS), with an estimated potential national cost of $40 billion. In our prior research, parents indicated that concerns about the impact of short stature on psychosocial function, both in childhood and projected into adulthood, have a major influence on their decision to seek medical care for a child's short stature. Yet thus far height has been the primary outcome measure of GH treatment, even though height is a poor predictor of psychosocial adjustment and health-related quality of life (QoL). The long- term goal of this research is to determine what drives better QoL and psychosocial adjustment in youth with short stature. While the prevailing assumption holds that the attainment of increased height directly provides benefit, we hypothesize that the impact of height on QoL and self-esteem is modified by characteristics of the parent and youth to a degree that exceeds the impact from height gain itself, with or without GH treatment. Thus, the proposed longitudinal mixed-methods study will follow for two years youth aged 8-14 years who undergo provocative GH testing in our Growth Center and a parent participant. Using semi-structured interviews and novel quantitative measures, Specific Aim 1 will explore youth and parent perceptions of short stature and its impact on QoL, perceptions and expectations vis-a-vis GH treatment, and decision-making regarding evaluation of short stature and GH treatment, with a focus on the youth's role in decision-making, which has not been studied but is critical in the context of an elective treatment (ISS) that is chronic (years), invasive (daily injections), and carries potential side effects. Using quantitative measures of both QoL and the positive aspects of self-esteem, Specific Aim 2 will describe trajectories of youth QoL and self-esteem for 2 years after provocative GH testing, including youth with GHD, ISS treated with GH, and ISS not treated with GH. Specific Aim 3 will define specific parent and youth characteristics that modify the relationship of height to QoL and self-esteem for those two years. The research proposed in this application will address a critical gap in our understanding of how patient and parent characteristics alter the potential impact of being short, and transform the currently held, traditional disease model of short stature into a richer framework that includes parent characteristics, parenting styles and youth characteristics as well as height. The proposed work will thereby lay the foundation for future definitive, long-term, randomized controlled trials testing the efficacy of GH or other interventions for short stature that include QoL and psychosocial adjustment as primary outcomes, and enable the field and clinical care to move forward in an evidence-based, value-driven way.